Use of Glucosamine
The use of pure glucosamine in the treatment of joint diseases is widely described in the patent as well as in the scientific literature, usually in combination with other compounds or extracts from various natural sources. Pure glucosamine is added as glucosamine hydrochloride or glucosamine sulphate, and comes from shellfish hydrolysis. For example, WO2000/0074696 describes “herbal compositions comprising glucosamine and Trypterygium wilfordii, Ligustrum lucidum and/or Erycibe schmidtii, for treating inflammation or degeneration of joint tissues, e.g. arthritis” where pure glucosamine is mixed with plant preparation. Other patents relate to compositions of plant carbohydrates as dietary supplements (EP 1 172 041 or EP 923 382) where glucosamine is originated from chitin, i.e. once again from shellfish hydrolysis.
The use of glucosamine as an anti-osteoarthritis agent has been intensively developed during the last decade. Glucosamine is suspected to be the sole active compound on joint disease such as osteoarthritis (up to recently only symptomatic treatment such as non-steroidal anti-inflammatory drugs have been sought to be efficient).
Glucosamine has also been shown preventing the cartilage degradation by inhibiting the production of MMPs (Matrix metalloproteases) such as MMP1, MMP3 and MMP13. Interestingly glucosamine is also related to the aging process of skin, which has been characterized mainly by the continuous loss of elasticity and the loss of moisture. Skin aging is reflected by major structural changes and variations in composition. Most notably aged skins have less collagen and glycosaminoglycans compared with young skins. Glycosaminoglycan molecules produced by the skin include hyaluronic acid (poly d-glucuronic acid-n-acetyl-d-glucosamine), chondroitin sulfate, and dermatan sulfate. Hyaluronic acid is produced in higher quantities by the skin cells in response to exfoliation. Hyaluronic acid has a large capacity for hydration.
Inhibiting MMP-1 is related to the inhibition of the polyglycan/collagen degradation, and therefore also related to skin ageing: MMP-1 can be induced by UV and is recognized as a marker of the skin ageing. In US 2002/119107, the invention is based on the selective inhibition of MMP-1 claiming topical compositions for protecting human skin from collagen degradation. US 2004/037901 claims a regime for inhibiting the adverse signs of effects of cutaneous aging comprising an extract from rosemary plant inhibiting the expression of metalloproteases.
Glucosamine has been shown to significantly improve dryness of the skin and exfoliation. Glucosamine increases the moisture content and improves the smoothness of the skin. These findings suggest that long-term intake of glucosamine is effective in improving moisture content and smoothness of the skin.
It has been shown that oral supplement containing glucosamine lead to a reduction (34%) in the number of visible wrinkles and (34%) in the number of fine lines in a group of women who took the supplement. The use of an oral supplement containing glucosamine, minerals, and various antioxidant compounds can potentially improve the appearance of visible wrinkles and fine lines.
U.S. Pat. No. 6,413,525 describes methods of substantially exfoliating the skin. In particular, the invention relates to topically applied compositions containing an amino sugar in the form of N-acetyl glucosamine: when young skin cells are exposed after exfoliation, they produce larger quantities of hyaluronic acid which is a glycosaminoglycan composed of a chain of alternating, repeating, D-glucuronic acid and N-acetyl-D-glucosamine molecules. N-acetyl-D-glucosamine is known to be a rate-limiting factor in the hyaluronic acid production by living cells. The topical application of glucosamine assists in the continued production of hyaluronic acid.
Other Compositions for topical application containing N-acetyl-D-glucosamine have also been disclosed for example, in JP 59 013 708 (soften and moisturize the skin) or U.S. Pat. No. 5,866,142 (a composition for exfoliating the skin).
Origin of Glucosamine
Glucosamine, 2-amino-2-deoxy-D-glucose, is a naturally occurring derivative of fructose and is an essential component of glycoproteins and proteoglycans, important constituents of many eukaryotic proteins. This is an essential component of mucopolysaccharides and chitin. Glycosaminoglycans (mucopolysaccharides) are large complexes incorporated into connective tissue, skin, tendons, ligaments and cartilage.
Industrial Sources of Glucosamine
Industrial glucosamine is a pure compound obtained from the acidic hydrolysis of chitin from shellfish, a complex carbohydrate derived from N-acetyl-D-glucosamine. As an example, U.S. Pat. No. 6,486,307 describes an improved method for chitin acidic hydrolysis: a method of producing glucosamine hydrochloride from chitin by grinding the chitin to a very fine size and digesting it with concentrated hydrochloric acid.
Glucosamine can also be produced from enzymatic hydrolysis of shellfish. As an example, U.S. Pat. No. 5,998,173 describes a novel process for directly producing N-acetyl-D-glucosamine from chitin utilizing an ensemble of the chitinase family of enzymes to hydrolyze chitin of crustacean shells.
Patents have also been filed protecting microbial fermentation processes where cultivated microorganisms biosynthesize glucosamine. As an example, U.S. Pat. No. 6,372,457 describes a method and material for producing glucosamine by fermentation using a genetically modified microorganism.
All these processes concern the production of pure, extracted glucosamine, in competition with shellfish extracts.
GB 649 791 relates to improvements in drying chicory. The process according to this patent comprises the steps of:                cutting chicory roots,        fermenting the chicory roots under aeraobic conditions at temperatures not substantially exceeding 70° C. (best temperatures between 50 and 55° C.) for 7 to 8 hours, and        quick drying chicory at 150° C. for about 30 minutes.        
These conditions do not allow to generate glucosamine.
Carvalho et al, in a publication entitled “inulin production by Vernonia herbacea as influenced by mineral fertilization and time of harvest” (Revista brasileira de botanica, 1998), showed that the addition of a fertilizer during cultivation of an inulin-containing plant does not enhance the inulin content.
In WO2005/053710, it has been found that glucosamine can be formed from several raw plant materials by following a special drying process, therefore obtaining glucosamine contents of between 150 and 1000 mg per kg dry weight.